Growth plate injuries result in growth arrest, formation of a “bony bar” and angular limb deformities in children. Novel therapeutic approaches directed towards prevention of bone formation and growth arrest have to integrate cellular grafts, biomaterials and growth factors with the ultimate goal of recapitulating the complex zonal organization of the growth plate. One endogenous source of cartilage progenitor cells is thought to be the resting zone of the growth plate. Until now, the lack of specific marker(s) for the resting zone restricted the examination of this population. In the proposed research, I aim to label and trace these cells during postnatal growth and in reaction to trauma, and I aim to understand: whether resting zone cells express skeletal stem cells characteristics (Aim 1), whether they are expandable and multi-potent (Aim 2) and whether they contribute to regeneration of the growth plate in a physeal fracture model (Aim 3). Clinical translation of chondrocyte stem cell regeneration necessitates basic validation in human tissue of the cell surface markers found in mouse stem cells. This last step in the project will be performed in collaboration with Dr. Fernando Santos Laboratory at University of Oviedo, Spain. Altogether, these results will provide a strong basis for development of bioengineering strategies for growth plate cartilage restoration. Finally, this collaboration between Dr Andreia Ionescu Lab and Dr Laboratory would provide not only an interchange between American and European laboratories, basic and clinical science, but also a robust criterion for identification of a stem cell population instrumental for the development of future therapeutics.
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